1. Field of the Invention
This invention pertains generally to cell and microparticle manipulation, and more particularly to optoelectronic tweezers (OET).
2. Description of Related Art
The ability to manipulate biological cells and micrometer scale particles plays an important role in many biological and colloidal science applications. However, conventional manipulation techniques, including optical tweezers, electrokinetic forces (electrophoresis, dielectrophoresis (DEP), traveling-wave dielectrophoresis), magnetic tweezers, acoustic traps, and hydrodynamic flows, cannot simultaneously achieve high resolution and high throughput.
DEP is a well established technique that has been widely used to manipulate micrometer and sub-micrometer particles as well as biological cells. Traveling-wave dielectrophoresis (TWD) is particularly attractive for high throughput cell manipulation without external liquid pumping. The traveling electric field produced by multi-phase alternating current (AC) bias on a parallel array of electrodes levitates and transports many particles simultaneously. However, the TWD cannot resolve individual particles. Recently, a programmable DEP manipulator with individually addressable two-dimensional electrode array has been realized using complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC) technology. Parallel manipulation of a large number (i.e., approximately 10,000) of individual cells was demonstrated. The CMOS DEP manipulator has two potential drawbacks. The need of on-chip IC increases the cost of the chip, making it less attractive for disposable applications. The trap density (i.e., approximately 400 sites/mm2) is also limited by the size of the control circuits.
Consequently, the use of electrokinetic forces and similar mechanisms provide high throughput, but lack the flexibility or the spatial resolution for controlling individual cells, or groups of cells. In addition, these techniques require structures formed through numerous lithographic steps.
Optical tweezers, however, offer high resolution for trapping single particles, yet provide limited manipulation area due to tight focusing requirements. The optical tweezers use direct optical force for the manipulating purpose, and require highly focused coherent light sources used with an objective lens having a high numerical-aperture (N. A.) value and a small field of view. To generate multiple optical traps or special optical patterns, it also requires techniques such as holography. These techniques require intense calculation for creating even simple optical patterns.
Accordingly a need exists for a particle and cell manipulation apparatus and method which provides parallel processing capability while still providing selectivity down to the single particle level. The present invention fulfills those needs, as well as others, and provides for manipulation of particles and cells at low light levels without the need of complex lithography or 3D beam control.